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尼加拉瓜19年儿科临床研究中登革热严重程度与血清型及免疫状态的关系

Dengue severity by serotype and immune status in 19 years of pediatric clinical studies in Nicaragua.

作者信息

Narvaez Federico, Montenegro Carlos, Juarez Jose G, Zambrana Jose Victor, Gonzalez Karla, Videa Elsa, Arguello Sonia, Barrios Fanny, Ojeda Sergio, Plazaola Miguel, Sanchez Nery, Camprubi Daniel, Kuan Guillermina, Paz-Bailey Gabriela, Harris Eva, Balmaseda Angel

出版信息

medRxiv. 2024 Jul 31:2024.02.11.24302393. doi: 10.1101/2024.02.11.24302393.

Abstract

BACKGROUND

Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease.

METHODS

This study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the relationship of serotype and immune status with dengue severity. Dengue cases were confirmed by molecular, serological, and/or virological methods, and sudy participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients.

RESULTS

We enrolled a total of 15,266 participants, of whom 3,227 (21%) were positive for DENV infection. Of 2,630 cases with serotype result by RT-PCR, 557 corresponded to DENV1, 992 to DENV2, 759 to DENV3 and 322 to DENV4. Severe disease was more prevalent among secondary DENV2 and DENV4 cases, while similar disease severity was observed in both primary and secondary DENV1 and DENV3 cases. According to the 1997 World Health Organization (WHO) severity classification, both DENV2 and DENV3 caused a higher proportion of severe disease compared to other serotypes, whereas DENV3 caused the greatest percentage of severity according to the WHO-2009 classification. DENV2 was associated with increased odds of pleural effusion and low platelet count, while DENV3 was associated with both hypotensive and compensated shock.

CONCLUSIONS

These findings demonstrate differences in dengue severity by serotype and immune status and emphasize the critical need for a dengue vaccine with balanced effectiveness against all four serotypes, particularly as existing vaccines show variable efficacy by serotype and serostatus.

摘要

背景

登革病毒是全球主要的健康威胁,由四种血清型(DENV1 - 4)组成,可导致从轻度到重度以及潜在致命疾病的一系列临床表现。

方法

本研究基于尼加拉瓜马那瓜的儿科登革热队列研究和儿科登革热医院研究的19年数据,调查血清型和免疫状态与登革热严重程度的关系。登革热病例通过分子、血清学和/或病毒学方法确诊,对6个月至17岁的研究参与者在住院期间或作为门诊患者进行随访。

结果

我们共招募了15266名参与者,其中3227人(21%)DENV感染呈阳性。在2630例通过逆转录 - 聚合酶链反应(RT - PCR)获得血清型结果的病例中,557例为DENV1,992例为DENV2,759例为DENV3,322例为DENV4。重症疾病在继发性DENV2和DENV4病例中更为普遍,而原发性和继发性DENV1和DENV3病例的疾病严重程度相似。根据1997年世界卫生组织(WHO)的严重程度分类,与其他血清型相比,DENV2和DENV3导致的重症疾病比例更高,而根据WHO - 2009分类,DENV3导致的重症比例最高。DENV2与胸腔积液几率增加和血小板计数低有关,而DENV3与低血压和代偿性休克有关。

结论

这些发现表明登革热严重程度因血清型和免疫状态而异,并强调迫切需要一种对所有四种血清型都具有平衡有效性的登革热疫苗,特别是因为现有疫苗在不同血清型和血清状态下显示出不同的效力。

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